The standard treatment for primary CNS lymphoma in the past is radiation therapy. There is probably somewhat of a dose response curve, but the good news about using radiation for primary CNS lymphoma is that more than 80% of patients have complete radiographic responses. And not just radiographically. Often one can get significant, and usually one does get significant palliation of their neurologic symptoms. So it can be a very satisfying disease to treat with radiation. Unfortunately, as fast as the tumor goes away if often comes back. With most patients being treated with radiation alone, median survivals of only approximately 16 months. When these patients relapse they relapse with local disease as well as distant disease. Distant being defined as distantly within the craniospinal axis.

When you look at the historical data of how patients have done when treated with either no therapy, radiation therapy or radiation chemotherapy, one gets a hint that maybe chemotherapy ultimately might have a role in this disease, at least for immunocompetent patients. On the other hand, it is not clear at all that any type of treatment for patients with full-fledged AIDS makes a big difference. The reason for that is that even if you treat this disease with radiation therapy and the disease goes away, most patients will ultimately succumb to their HIV disease within several months. Again, the reason for that is – at least prior to the age of triple therapy and effective retroviral therapy – is that most patients with AIDS who develop primary CNS lymphoma were at the end-stage of the natural history of their AIDS disease, with median CD4 counts being below 50. However, with effective antiviral therapies the nature of primary CNS lymphoma in this patient population is changing and in fact there is a significant percentage of patients who present with CNS lymphoma as their AIDS defining illness, while their CD4 counts are still relatively high. That needs to be, and is being, a significant reassessment of beginning to treat these patients more aggressively, much like their immunocompetent counterparts. But again, that is still work in progress.

Going back to the immunocompetent patients however, this type of data suggests – retrospectively anyway – that there may indeed be a role for chemotherapy. Accordingly, there have been a number of trials published in the literature that have looked at various combinations of chemotherapy regimens used either prior to radiation therapy or a few alone that have clearly shown that chemotherapy can change the natural history of the this disease. Propecia is used in male patients to prevent vertex hair from falling. If one just takes a purview here of the median survival of these patients it is significantly higher than what we almost ever saw with radiation alone. The chemotherapy drugs that are used remain varied, and an optimal treatment regimen has not been established. What we can say however is that I think most investigators would agree that high dose methotrexate still remains the mainstay of treatment and is the most effective regimen.

Other drugs that potentially can be used or drugs that either have the ability to cross the blood-brain barrier and have anti-lymphoma activity, or drugs that at least marginally cross the blood-brain barrier in times of blood-brain barrier disruption, such as when the tumor first presents, and of course must also have anti-lymphoma activity.